Natural killer cells inhibit breast cancer cell invasion through downregulation of urokinase‑type plasminogen activator

Jin, Hao; Choi, Hyojeong; Kim, Eun‐Sook; Lee, Hwan Hee; Cho, Hyosun; Moon, Aree

doi:10.3892/or.2020.7840

Cited by 9 publications

(9 citation statements)

References 35 publications

(39 reference statements)

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“…NK cell activation can detect tumor cells, leading to tumor cell apoptosis (45). The aggressive biological behavior of triple-negative breast cancer is inhibited through IL-6 secreted by infiltrating NK cells (46). It has also been reported that low NK cell infiltration could predict poor survival (47).…”

Section: Discussionmentioning

confidence: 99%

MKL1 is a key biomarker correlated with immune infiltrates and chemosensitivity in breast cancer

Hua

Yang

2021

Bosn J of Basic Med Sci

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Megakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas (TCGA) breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer (NK) cells, macrophages, neutrophils and dendritic cells (DCs). The chromatin modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer.

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Section: Discussionmentioning

confidence: 99%

MKL1 is a key biomarker correlated with immune infiltrates and chemosensitivity in breast cancer

Hua

Yang

2021

Bosn J of Basic Med Sci

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“…Natural killer cells in the TME prevent cell invasion by down-regulating urokinase-type fibrinogen activator. 31 Previous research has indicated that NK cells could regulate cancer progression, hence attracting significant interest in the genes associated with these cells. 32 However, the molecular mechanisms underlying the antitumor activity of NK cells remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…These types of cancer are associated with a higher percentage of NK cells in the TME. Natural killer cells in the TME prevent cell invasion by down‐regulating urokinase‐type fibrinogen activator 31 . Previous research has indicated that NK cells could regulate cancer progression, hence attracting significant interest in the genes associated with these cells 32 .…”

Section: Discussionmentioning

confidence: 99%

Prognosis and therapy in thyroid cancer by gene signatures related to natural killer cells

Jin,

Han,

Zhang

et al. 2024

The Journal of Gene Medicine

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BackgroundNatural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell‐related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell‐related genes for predicting thyroid cancer (THCA).MethodsThe single‐cell RNA sequencing (scRNA‐seq) data from seven THCA samples (GSE184362) and bulk‐RNA‐seq data of 502 THCA patients (TCGA‐THCA) were included. The scRNA‐seq data was analyzed using the “Seurat” R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package “ConsensusClusterPlus”. The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta‐cohort. In the TCGA‐THCA cohort, the “glmnet” R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The “maftools” R package was used to examine the somatic mutation landscape of THCA in both low‐ and high‐risk groups.ResultsOne‐hundred and eighty‐five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA‐THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low‐risk H‐TMB+ group had a better prognosis, while the high‐risk L‐TMB+ group had the worst prognosis.ConclusionNatural killer cell‐related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.

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“…uPA has been involved in several physiological and pathological procedures, including cell invasion, tumor growth, and metastasis [30,[36][37][38][39]. Calcitonin-mediated inhibition of MDA-MB-231 cell invasion depended on the downregulation of uPA [40].…”

Section: Discussionmentioning

confidence: 99%

“…We examined the possible involvement of PAI-1, an inhibitor of uPA [30], in CA-5f-induced uPA downregulation. The protein level of PAI-1 in Hs578T cells was markedly increased by treatment with CA-5f (Fig.…”

Section: Ca-5f Reduces Protein Expression Of Proand Active-upa Possibly By Upregulating Pai-1mentioning

confidence: 99%

A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells

Kim

Moon

2021

Toxicol Res.

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Triple-negative breast cancer (TNBC) is one of the most aggressive types of breast cancer with poor outcomes. Patients with TNBC cannot benefit from targeted therapies such as Tamoxifen and Herceptin. The aim of the present study was to seek a preventive or therapeutic agent with a potential inhibitory effect on aggressive progression of TNBC. Anticancer effect of a natural compound curcumin have been demonstrated, however, development of more effective curcumin analogs with better bioavailability is needed. We investigated if a curcumin analog CA-5f could inhibit the invasive phenotype of TNBC cell lines in the present study. Treatment with CA-5f inhibited the viability of MDA-MB-231 and Hs578T TNBC cells, possible by inducing apoptosis. The invasive phenotypes of these cells were inhibited by CA-5f in a concentration-dependent manner. Protein expression of urokinase-type plasminogen activator (uPA), a serine protease known to degrade the extracellular matrix and lead to invasion, was markedly decreased by CA-5f in Hs578T cells. However, mRNA level of uPA was not altered by CA-5f, implicating that the effect of CA-5f was not through transcriptional regulation. Of note, CA-5f upregulated plasminogen activator inhibitor type (PAI)-1, which is known to inhibit uPA by interacting with urokinase-type plasminogen receptor, in TNBC cells. Taken together, these results demonstrated that CA-5f significantly inhibited the invasive phenotype of TNBC cells, possibly by decreasing the protein level of uPA through upregulating PAI-1. Our results may provide useful information on developing CA-5f as a potential therapeutic agent against malignant progression of TNBC.

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Natural killer cells inhibit breast cancer cell invasion through downregulation of urokinase‑type plasminogen activator

Cited by 9 publications

References 35 publications

MKL1 is a key biomarker correlated with immune infiltrates and chemosensitivity in breast cancer

MKL1 is a key biomarker correlated with immune infiltrates and chemosensitivity in breast cancer

Prognosis and therapy in thyroid cancer by gene signatures related to natural killer cells

A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells

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